Computing Systems

DB: Just to start off very basically, what got you interested in science,
in general?

DE: When I don’t understand how things work, I’m curious.
It bothers me when I don’t understand how things work. I’d like
to understand how things work. I want to understand how things work. I can repeat
that for a long time.

DB: So what got you into synthetic biology, specifically?

DE: So…I’d like to understand how biology works, how living
organisms work. so I started thinking about why it’s been so hard to understand
biology. And the conclusion I’ve come to, which is a very preliminary
conclusion that we have to test, is that the biological systems that we find
in nature are not themselves designed by nature, by evolution, to be easy to
understand. And so if I wanted to have biology that I understand, I’d
be better off building it myself. In the same way that you might try to understand
a car, or a bicycle by taking it apart and having the pieces all over your lawn.
But you’re going to have a much better understand of a car or a bicycle
if you take the bits and pieces and put them together to build one from scratch.
And that’s why I got interested in synthetic biology.

DB: So that takes us in the next direction. How would you define synthetic
biology? What is it, and what does it actually synthesize?

DE: There’s a couple different ways to look at it. I mean, for
me, I’m trained as an engineer, so my interest is to be able to routinely
and reliably, quickly, easily, cheaply put together the bits and pieces of biology
to make new and useful things. The goal of synthetic biology is to make routine
the engineering, the programming of living organisms. So you think about how
you’d use a computer today, how you program a computer today, even though
it might sound like a challenging thing to do, in relative and absolute terms
it’s quite easy to program a computer. So how do we get to some future
where the programming of living systems by changing their DNA and other things
is as simple and straightforward and understandable and reliable as the computers
are today? So that’s my take on synthetic biology. It’s a combination
of : what are the things we’d actually like to get biology to do on our
behalf, combined with: what are the tools, technology platforms, the basic infrastructure
that would help us get to that endpoint more reliably, and let more people get
there. There’s another perspective on the field, which is not an engineering
perspective. The scientific perspective on the field is, “I don’t
understand something unless I can put it together.” And the last seventy
years of biology has been a tremendous success at taking things apart and reading
out the genome, but we’ve never put things back together. Again, we can
go back to the idea that you take your father’s car, you rip it apart,
it’s all over the lawn, you sort of understand what’s going on,
but until you can put it back together, you’re not going to convince anybody
that you really understand what you’re doing.

DB: What part of that do you think makes synthetic biology such a hot
field right now, makes it so popular?

DE: It’s fun. You get to build stuff. Right, I mean, and, as mentioned
before, building is a great way to learn. You might fail, you might not succeed,
but you’re going to be succeeding for reasons that are physical reasons
which you can go follow up on. The other thing to say is 70 years ago, it was
the physicists who came into biology and really shook things up. I suspect that
what’s happening now is that the engineers are coming into biology, and
they’re going to shake things up in a complementary, different way, but
as significant. And if you ask an engineer what they want to do in their heart,
they want to make something. The other, last thing to say is that we’ve
developed some technologies that make it easy. Not easy, I mean easier. DNA
synthesis is getting better, and better, and better, which means that the cost
and time to compile one of your designs isn’t six years. It might be six
weeks. Which is still slow, but it’s not infinitely slow. We have things
like the registry of standard biological parts, as a tool for organizing information
about the different bits and pieces. And we’ve created a community, where
people now can talk to one another and have fun with what they’re doing.
So it’s a combination of basic science, combined with foundational technologies,
combined with a celebration of the work, that’s sort of letting things
happen.

DB: So, with these decreasing down times between projects and so on,
how do you see synthetic biology changing the world as we know it, in the future,
once it’s become more widely used and faster, and cheaper?

DE: Well, it’s already possible to redesign genomes. So you can
take a genome from a natural, biological system and do a systematic redesign
on it. A group in Japan last year took the genome of one organism and moved
it into another organism. So what are you going to do with that capability?
You could start to redesign approximately any organism you want. What’s
the impact of that? Lot’s of things we can imagine: Genomes that are designed
to be understandable. Genomes whose evolution is directed by their designers
as opposed to by nature. Imagine how that impacts health and medicine. Imagine
the societal conversations around the applications of that technology. So that’s
one off the top example. The other thing is that biology isn’t only about
health and medicine. Biology can be viewed from an engineer’s perspective
as a technology platform for doing all sorts of stuff. So this wood on the desk
is made by biology, the material that I’m wearing is made by biology,
chemicals that I’m eating are made by biology, the energy comes from biology.
So biological systems are really good at material construction, chemical production,
energy production, information processing, yadda yadda yadda. What happens when
we get better at programming living systems to do those things on our behalf?
The problem with the question is that it’s very quickly to talk about
these applications that are kind of like science fiction, and the trick, then,
is to map them into some path where we can make incremental progress towards
those goals. And I think what you’re seeing right now is that much of
the thinking and investment in research community is how to make all of this
easier, so that we can try more stuff more quickly. It’s investing in
the foundational infrastructure.

DB: You said that you were trained as a structural engineer, and one
of the big emphases of synthetic and computation biology is that you really
are at the crossroads of a lot of different fields. Can you describe a little
what it’s like to have things coming in from so many different fields?

DE: It’s nice to be able to learn from different communities.
Everybody views the world form a slightly different perspective, and sometimes
there’s enough people that gather around one perspective to become a field,
or a community. Biology, civil engineering, electrical engineering, chemistry,
physics, mathematics, computer science. The great reward of being able to pass
between perspectives and groups is that it forces you to confront the biases
and gross approximations in any one group. And that’s tremendously rewarding.

DB: What gave you the idea to make the comic strip?

DE: So I was out at a meeting in Los Angeles, and half the people at
the meeting were artists, and half the people at the meeting were scientists,
and engineers. Researchers. And the purpose of the meeting was to think about
imagery and visualization in the context of research. The meeting was organized
by Felice Frankel, who’s this amazing scientific photographer. She’s
got this book, Envisioning Science. What Felice did in organizing this meeting
was, she asked everybody to send in a picture that was representative of their
work, and they would be printed up on the nametags. So, I’m walking around
the first day of the meeting, and I’ve got my picture. I had put a picture
of a genetic device that we had been using in classes to try to teach this concept
of how to define genetic devices. I was very proud of this picture of this genetic
device on my nametag. So this guy comes up to me and he’s all excited,
and he’s like, “Hi! What’s that?” And I’m like,
“Well, do you know anything about DNA?” And he says, “Oh,
yeah. “”Well, it’s a genetically encoded inverter.”
And he said “Cool, tell me how it works!” Where an inverter is just
this device. I tell him the story about how a genetically encoded inverter works.
I finish my story, and he goes, “That sucks!” And I’m like
“What?” “That’s horrible.” I go “What d’ya
mean?” And he said “You just told me a story for how that device
works, but what you have on your nametag is an image. So it’s an image,
but it has no meaning. You need a comic.”And I’m like “Who
are you?” He says, “Oh, my name’s Larry Gonick, I wrote the
Cartoon Guide for Genetics.” Which is this great guidebook for genetics.
And I was like, “Yeah, alright, how do I make a comic?” He said
“You just go make one.” So on the way home I sketched out the comic
strip, and then my assistant here is also a screenwriter, and she happened to
know the guy who does the storyboards for Spider-Man. When she saw my initial
sketches, she said they suck, and we convinced Chuck, the illustrator out in
Los Angeles, to do the drawings for us. Hopefully, it’s a teaching tool,
but I have no idea if it works or not. So people should check it out and give
me feedback.

DB: If you hadn’t gone into synthetic biology, what do you think
you would be doing right now?

DE: Surfing. I don’t know. Writing poetry? Writing poetry and
surfing. But probably in the other order.

DB: The last question is, for our potential listeners and definite readers
who are interested in computational biology, and systems and synthetic biology,
do you have any advice for aspiring scientists in general, for people who want
to go into this kind of field?

DE: In biology? In the areas you listed?

DB: In biology, but really in science in general. To someone who’s
saying, “Oh, I really like science.” And they’re a senior
in high school. Is there anything they ought to know, any advice you have?

DE: When you encounter research in biology, it’s oftentimes so
far removed from the physical consideration of the organism. whenever you’re
thinking about biology, think about it in the context of it’s a physical
object that has to be doing something in the three-dimensional world. The other
thing to say is people express great wonderment, and excitement, and almost
a magical relationship with the living world. And it’s a great, appropriate
perspective to have. But I think over the coming years, faster than most expect,
we’ll see a transition in biology where it becomes much simpler and easier
to engineer things, to engineer new living systems. And we don’t actually
know how to do that right now, but there are lessons buried in the lore and
wisdom of other engineering disciplines. So some appreciation of the tools of
engineering—instead of celebrating biological complexity, which is what
scientists often want to do, an engineer would strive for simplicity. That sounds
almost Zen, I don’t mean it that way. But instead of just imagining the
world as it exists and as we inherit it from nature, I think it’s becoming
increasingly important that we understand how to imagine worlds that might be,
how we would choose how to design and construct them.

DB: Well, thank you so much for talking to me. It’s been a real
pleasure.